Despite the epidemiological reality of ongoing HIV infection in Puerto Rico, the public health infrastructure related to HIV/AIDS and substance abuse in the territory is severely lacking, as reflected in alarmingly high rates of morbidity/mortality among people who inject drugs (PWID). Because of this, HIV continues to have substantial impact on individual health and the healthcare system in Puerto Rico. While Puerto Rico ranks in the top 5% of US states and territories with respect to HIV prevalence, San Juan ranks only in the top 20% of metropolitan areas. This discrepancy points to a different type of epidemic, where rural communities contribute disproportionately to HIV prevalence rates relative to urban areas. The dynamics of HIV among PWID in rural Puerto Rico remains largely unknown, though HIV risk is known to increase precipitously upon migration to the mainland-a journey that has become the norm for PWID in need of services. Understanding the dynamics of rural HIV infection is critical to developing effective cost-efficient prevention strategies using he most recent developments in epidemiology, prevention, and treatment. This project applies both quantitative and qualitative methods to characterize and address HIV propagation dynamics in rural PWID networks of Central Puerto Rico. This is achieved by: (i) characterizing demographics, disease prevalence, and behaviors of at-risk populations in four rural communities via analysis of respondent- driven sampling surveys; (ii) modeling the dynamic structure of risk partnerships within the rural communities via ethnographically validated network micro-assays, (iii) developing stochastic computer simulations of artificial (but statistically plausible) dynamic risk networks, via models of the real-world data collected; (iv) identifying which behavioral and structural variables most strongly impact HIV/HCV epidemiology in these rural settings, via sensitivity analysis of simulation outcomes; (v) evaluating the relative efficay and cost efficiency of a range of evidence-based HIV control strategies within the target population via augmented simulations. The project addresses lack of link-to-care for the PWID population by (1) developing a working relationship with local private infectious disease doctors in all four municipalities to enhance access to care by immediately linking study participants who test positive for HIV or HCV to services; (2) developing an PWID escort system to ensure access and treatment throughout the life of the project, (3) developing new ways to support testing and treatment enrollment for this population using a social network approach that builds upon peer-driven community education and advocacy programs to slow the spread of the HIV/HCV in rural Puerto Rico; and finally, in concert with a Dissemination Advisory Board comprised of local stakeholders, (4) disseminating the simulation-based findings concerning optimal evidence-based HIV control strategies that are most likely to be effective and cost-efficient in addressing disease propagation in rural Puerto Rico. 1